OBJECTIVETo investigate whether oxymatrine (OM) could promote mesenchymal stem cell (MSC) therapy in CCl4-induced hepatic fibrosis (HF) in rats and to initially explore its mechanisms.

METHODSTotally 50 male SD rats were randomly divided into five groups,i.e., the normal control group, the model group, the MSC therapy group, the OM therapy group, and the MSC combined OM therapy group, 10 in each group. Except the normal control group, the HF model was duplicated by CCl4 induction. After successful modeling, rats in the MSC therapy group received 5 x10(6) MSCs by intravenous injection via caudal vein, once a week. Rats in the OM therapy group received 50 mg/kg OM by intramuscular injection, three times a week. Rats in MSC combined OM therapy group received 5 x 10(6) MSCs by intravenous injection via caudal vein, once a week and 50 mg/kg OM by intramuscular injection three times a week. Equal volume of normal saline was given to those in the normal control group and the model group. All medication lasted for 8 weeks. Serum levels of ALT and AST were detected 8 weeks later. The hepatic histopathological injury and extracellular matrix deposit were assessed using HE and Masson staining. Expressions of serum interleukin-4 (IL-4) and interleukin-10 (IL-10) were detected using enzyme linked immunosorbent assay (ELISA).

RESULTS(1) Compared with the normal control group, serum levels of ALT and AST significantly increased in the model group (P < 0.05). Compared with the model group, serum levels of ALT and AST significantly decreased in the OM therapy group, the MSC therapy group, and the MSC combined OM therapy group at the end of 8 weeks of treatment (P < 0.05). But serum levels of ALT and AST were significantly lower in the MSC combined OM therapy group than in the OM therapy group and the MSC therapy group (P < 0.05). (2) Compared with the model group, the hepatic injury was significantly lessened and the area of extracellular matrix deposit was significantly reduced in the OM therapy group, the MSC therapy group, and the MSC combined OM therapy group (P < 0.05). Besides, they wer more significant in the MSC combined OM therapy group (P < 0.05). (3) Compared with the model group, the serum IL-4 level was significantly higher in the MSC therapy group and the MSC combined MO group (P < 0.05). It was higher in the MSC combined MO group (P < 0.05). Although the serum IL-4 level also increased in the OM therapy group, but with no statistical difference (P > 0.05). (4) The serum IL-10 level significantly increased in the OM therapy group, the MSC therapy group, and the MSC combined OM therapy group (P < 0.05), and it was the highest in the MSC combined OM therapy group among the three groups (P < 0.05). (5) Two-photon fluorescence imaging showed no signals of MSCs in liver with or without OM injection.

CONCLUSIONOM could promote mesenchymal stem cell therapy in hepatic fibrosis rats, which might be involved in increasing serum levels of IL-4 and IL-10.